| DOI | Trouver le DOI : https://doi.org/10.1016/j.bmc.2008.06.023 |
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| Auteur | Rechercher : Prakesch, Michael; Rechercher : Denisov, Alexey Yu; Rechercher : Naim, Marwen; Rechercher : Gehring, Kalle; Rechercher : Arya, Prabhat1 |
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| Affiliation | - Conseil national de recherches du Canada. Institut Steacie des sciences moléculaires du CNRC
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| Format | Texte, Article |
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| Sujet | apoptosis; Bcl-2 family; chemical biology; combinatorial chemistry; diversity-oriented synthesis; high-throughput synthesis; Mcl-1; natural product-inspired probes; protein-protein interactions; small molecule-protein interactions by NMR |
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| Résumé | A tetrahydroaminoquinoline-based library was generated with the goals of finding small molecule modulators of protein-protein interactions. Several library members as well as other related intermediates were tested for their ability to bind to Bcl-XL and Mcl-1 by in silico and 15N NMR studies. The NMR study led to the identification of the tetrahydroaminoquinoline-based nude scaffold, 7 as a weak binder (Kd?=?200?[mu]M for Bcl-XL and Kd?=?300?[mu]M for Mcl-1) to both proteins. Using this scaffold as the starting material, we then synthesized a focused library of only 9 derivatives by applying the principles of a fragment-based approach. All these derivatives were then tested by NMR and this led to the discovery of a novel, small molecule (MIPRALDEN, 17) as a binder to Mcl-1 and Bcl-XL (KD?=?25 and 70?[mu]M). This finding is novel because to our knowledge there are not many small molecules known in the literature that bind to Mcl-1. |
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| Date de publication | 2008-06-18 |
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| Dans | |
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| Langue | anglais |
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| Numéro NPARC | 12338876 |
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| Exporter la notice | Exporter en format RIS |
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| Signaler une correction | Signaler une correction (s'ouvre dans un nouvel onglet) |
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| Identificateur de l’enregistrement | f1e17f7e-473f-4663-9a5b-8bd20e7ba751 |
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| Enregistrement créé | 2009-09-11 |
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| Enregistrement modifié | 2020-04-15 |
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